title: IL-23 receptor expression on γδ T cells correlates with their enhancing or suppressive effects on autoreactive T cells in experimental autoimmune uveitis.
abstract: We have previously reported that, depending on their activation status, mouse γδ T cells can either enhance or inhibit the activity of IL-17(+) autoreactive T cells in experimental autoimmune uveitis. In this study, we showed that γδ T cells in naive C57BL/6 (B6) mouse do not express the IL-23R, whereas in immunized mice, it is expressed on >50% of γδ T cells. In vitro studies showed that IL-23R expression on γδ T cells is modulated by their state of activation, as weakly activated γδ T cells expressed the IL-23R, but highly activated γδ T cells did not. Functional studies showed that IL-23R(+) γδ T cells had the strongest suppressive effect on IL-17(+) autoreactive T cells, and that this effect was inhibited when the IL-23R was blocked by anti-IL-23R Ab or in the presence of excessive amounts of exogenous IL-23. We conclude that the balance between the enhancing and inhibitory effects of γδ T cells is regulated by their level of IL-23R expression. The expression of variable IL-23R levels allows γδ T cells to have different regulatory effects on adaptive immune responses, conceivably as a result of αβ and γδ T cells competing for IL-23.
authors.affiliation: Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Liang
authors.forename: Aijun
authors.initials: A
authors.lastname: Zuo
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology*
chemical_list: D000906:Antibodies; D020381:Interleukin-17; D053759:Interleukin-23; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; C528688:interleukin-23 receptor, mouse